HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RAG1
recombination activating 1
Chromosome 11 Β· 11p12
NCBI Gene: 5896Ensembl: ENSG00000166349.11HGNC: HGNC:9831UniProt: P15918
157PubMed Papers
24Diseases
0Drugs
171Pathogenic Variants
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingV(D)J recombinationprotein autoubiquitinationubiquitin-protein transferase activityOmenn syndromesevere combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positivecombined immunodeficiency with skin granulomascombined immunodeficiency due to partial RAG1 deficiency
✦AI Summary

RAG1 is the catalytic component of the RAG recombinase complex essential for V(D)J recombination in developing B and T lymphocytes 1. RAG1 mediates DNA binding to conserved recombination signal sequences (RSS) and catalyzes double-strand DNA breaks between RSS and coding segments through a two-step nicking and hairpinning mechanism, generating the structural diversity of immunoglobulin and T-cell receptor genes 2. Beyond endonuclease activity, RAG1 functions as an E3 ubiquitin-protein ligase that monoubiquitinates histone H3, a modification required for the joining phase of V(D)J recombination. RAG1 also enforces allelic exclusion by inducing ATM-dependent repositioning of unrearranged immunoglobulin alleles to heterochromatin, ensuring single B-cell receptor expression 2. Pathogenic RAG1 mutations cause a spectrum of primary immunodeficiencies ranging from severe combined immunodeficiency (SCID) to delayed-onset disease with autoimmunity and granulomas 2. Notably, residual recombination activity of mutant RAG1 proteins correlates with disease severity, enabling phenotype prediction 2. Currently, hematopoietic stem cell transplantation remains the only cure for severe RAG1 deficiency, though emerging gene therapy approaches using viral vectors or CRISPR/Cas9-mediated correction show clinical promise 3. CRISPR/Cas9 gene editing strategies targeting in-frame exon 2 integration achieve physiologic RAG1 expression and functional rescue in patient-derived cells 4.

Sources cited
1
RAG1 and RAG2 are lymphocyte-specific recombinase components involved in V(D)J recombination for antigen receptor diversity generation
PMID: 27083993
2
RAG1 catalyzes DNA cleavage in V(D)J recombination; mutations cause various immunodeficiencies; residual activity correlates with disease severity
PMID: 24290284
3
Gene therapy with viral vectors and CRISPR/Cas9 are emerging alternatives to HSCT for RAG1 deficiency treatment
PMID: 39303994
4
CRISPR/Cas9-mediated in-frame exon 2 insertion drives physiologic RAG1 expression and rescues immunodeficiency in patient cells
PMID: 38324638
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜24
Omenn syndromeOpen Targets
0.81Strong
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.81Strong
combined immunodeficiency with skin granulomasOpen Targets
0.78Strong
combined immunodeficiency due to partial RAG1 deficiencyOpen Targets
0.69Moderate
recombinase activating gene 1 deficiencyOpen Targets
0.65Moderate
Combined immunodeficiency T+ B+ due to partial RAG1 deficiencyOpen Targets
0.64Moderate
severe combined immunodeficiencyOpen Targets
0.56Moderate
histiocytic medullary reticulosisOpen Targets
0.55Moderate
T-B- severe combined immunodeficiencyOpen Targets
0.53Moderate
T-B+ severe combined immunodeficiencyOpen Targets
0.53Moderate
T+ B+ severe combined immunodeficiencyOpen Targets
0.53Moderate
central nervous system cancerOpen Targets
0.34Weak
tumor predisposition syndrome 3Open Targets
0.34Weak
immunodeficiency diseaseOpen Targets
0.33Weak
cardiomyopathyOpen Targets
0.29Weak
Pelizeaus-Merzbacher spectrum disorderOpen Targets
0.27Weak
Sudanophilic leukodystrophyOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
microcephalyOpen Targets
0.14Weak
primary ciliary dyskinesiaOpen Targets
0.12Weak
Alpha/beta T-cell lymphopenia, with gamma/delta T-cell expansion, severe cytomegalovirus infection and autoimmunityUniProt
Combined cellular and humoral immune defects with granulomasUniProt
Omenn syndromeUniProt
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positiveUniProt
Pathogenic Variants171
NM_000448.3(RAG1):c.999T>A (p.Tyr333Ter)Pathogenic
not provided|Combined immunodeficiency with skin granulomas;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Recombinase activating gene 1 deficiency|Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
β˜…β˜…β˜…β˜†2024β†’ Residue 333
NM_000448.3(RAG1):c.2095C>T (p.Arg699Trp)Likely pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Histiocytic medullary reticulosis|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Combined immunodeficiency due to partial RAG1 deficiency|Recombinase activating gene 1 deficiency|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency due to partial RAG1 deficiency;Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis
β˜…β˜…β˜…β˜†2024β†’ Residue 699
NM_000448.3(RAG1):c.2814T>G (p.Tyr938Ter)Likely pathogenic
Severe combined immunodeficiency, B cell-negative|Recombinase activating gene 1 deficiency
β˜…β˜…β˜…β˜†2024β†’ Residue 938
NM_000448.3(RAG1):c.2877G>A (p.Trp959Ter)Pathogenic
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Recombinase activating gene 1 deficiency
β˜…β˜…β˜…β˜†2024β†’ Residue 959
NM_000448.3(RAG1):c.424C>T (p.Arg142Ter)Pathogenic
Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency due to partial RAG1 deficiency|Combined immunodeficiency with skin granulomas;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Histiocytic medullary reticulosis|Recombinase activating gene 1 deficiency|Combined immunodeficiency due to partial RAG1 deficiency|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Combined immunodeficiency with skin granulomas
β˜…β˜…β˜…β˜†2023β†’ Residue 142
NM_000448.3(RAG1):c.256_257del (p.Lys86fs)Pathogenic
Combined immunodeficiency with skin granulomas;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|not provided|RAG1-related disorder|Combined immunodeficiency due to partial RAG1 deficiency|Severe combined immunodeficiency disease|Histiocytic medullary reticulosis|Recombinase activating gene 1 deficiency|Combined immunodeficiency due to partial RAG1 deficiency;Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
β˜…β˜…β˜…β˜†2023β†’ Residue 86
NM_000448.3(RAG1):c.1331C>T (p.Ala444Val)Pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Recombinase activating gene 1 deficiency|Combined immunodeficiency due to partial RAG1 deficiency|Severe combined immunodeficiency disease
β˜…β˜…β˜…β˜†2023β†’ Residue 444
NM_000448.3(RAG1):c.775del (p.Ser259fs)Pathogenic
not provided|Histiocytic medullary reticulosis|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Combined immunodeficiency due to partial RAG1 deficiency|Recombinase activating gene 1 deficiency|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Histiocytic medullary reticulosis;Combined immunodeficiency with skin granulomas;Combined immunodeficiency due to partial RAG1 deficiency
β˜…β˜…β˜…β˜†2023β†’ Residue 259
NM_000448.3(RAG1):c.2487_2488delinsTT (p.Arg829_Lys830delinsSerTer)Pathogenic
Combined immunodeficiency due to partial RAG1 deficiency|not provided|Combined immunodeficiency with skin granulomas;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Recombinase activating gene 1 deficiency|Combined immunodeficiency due to partial RAG1 deficiency;Histiocytic medullary reticulosis;Combined immunodeficiency with skin granulomas;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
β˜…β˜…β˜…β˜†2023β†’ Residue 829
NM_000448.3(RAG1):c.1677G>T (p.Arg559Ser)Pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Severe combined immunodeficiency disease|Histiocytic medullary reticulosis
β˜…β˜…β˜†β˜†2026β†’ Residue 559
NM_000448.3(RAG1):c.1871G>A (p.Arg624His)Pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Combined immunodeficiency due to partial RAG1 deficiency|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency due to partial RAG1 deficiency;Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
β˜…β˜…β˜†β˜†2026β†’ Residue 624
NM_000448.3(RAG1):c.1566G>T (p.Trp522Cys)Pathogenic
Combined immunodeficiency with skin granulomas|not provided|Combined immunodeficiency with skin granulomas;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive|Combined immunodeficiency due to partial RAG1 deficiency|Combined immunodeficiency due to partial RAG1 deficiency;Combined immunodeficiency with skin granulomas;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Histiocytic medullary reticulosis
β˜…β˜…β˜†β˜†2026β†’ Residue 522
NM_000448.3(RAG1):c.1420C>T (p.Arg474Cys)Pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Combined immunodeficiency due to partial RAG1 deficiency|Combined immunodeficiency with skin granulomas
β˜…β˜…β˜†β˜†2026β†’ Residue 474
NM_000448.3(RAG1):c.1187G>A (p.Arg396His)Pathogenic
Histiocytic medullary reticulosis|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Combined immunodeficiency due to partial RAG1 deficiency|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis;Combined immunodeficiency due to partial RAG1 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 396
NM_000448.3(RAG1):c.1303A>G (p.Met435Val)Pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency due to partial RAG1 deficiency;Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Severe combined immunodeficiency disease|Combined immunodeficiency due to partial RAG1 deficiency|RAG1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 435
NM_000448.3(RAG1):c.1870C>T (p.Arg624Cys)Pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Combined immunodeficiency due to partial RAG1 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 624
NM_000448.3(RAG1):c.1421G>A (p.Arg474His)Pathogenic
not provided|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Severe combined immunodeficiency disease|Histiocytic medullary reticulosis|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency due to partial RAG1 deficiency;Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis|Combined immunodeficiency due to partial RAG1 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 474
NM_000448.3(RAG1):c.612G>A (p.Trp204Ter)Pathogenic
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Severe combined immunodeficiency disease|Combined immunodeficiency due to partial RAG1 deficiency;Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Histiocytic medullary reticulosis;Combined immunodeficiency with skin granulomas
β˜…β˜…β˜†β˜†2026β†’ Residue 204
NM_000448.3(RAG1):c.2923C>T (p.Arg975Trp)Pathogenic
Combined immunodeficiency with skin granulomas|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Severe combined immunodeficiency disease|Combined immunodeficiency due to partial RAG1 deficiency|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
β˜…β˜…β˜†β˜†2026β†’ Residue 975
NM_000448.3(RAG1):c.2924G>A (p.Arg975Gln)Pathogenic
not provided|Severe combined immunodeficiency disease|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency with skin granulomas|Combined immunodeficiency due to partial RAG1 deficiency|Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;Combined immunodeficiency due to partial RAG1 deficiency;Combined immunodeficiency with skin granulomas;Histiocytic medullary reticulosis|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2025β†’ Residue 975
View on ClinVar β†—
Related Genes
CD8AProtein interaction100%IFNGProtein interaction99%PTPRCProtein interaction98%FOXP3Protein interaction98%IL2Protein interaction98%IL17AProtein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
11%
Liver
9%
Ovary
4%
Lung
4%
Brain
2%
Gene Interaction Network
Click a node to explore
RAG1CD8AIFNGPTPRCFOXP3IL2IL17A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P15918
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.70LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.40–0.70]
RankingsWhere RAG1 stands among ~20K protein-coding genes
  • #2,871of 20,598
    Most Researched157 Β· top quartile
  • #433of 5,498
    Most Pathogenic Variants171 Β· top 10%
  • #5,356of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedRAG1
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency.
PMID: 24290284
J Allergy Clin Immunol Β· 2014
1.00
2
NAD metabolism fuels human and mouse intestinal inflammation.
PMID: 28877980
Gut Β· 2018
0.90
3
Gene therapy strategies for RAG1 deficiency: Challenges and breakthroughs.
PMID: 39303994
Immunol Lett Β· 2024
0.80
4
IL-17A-producing CD8
PMID: 36759154
Gut Β· 2023
0.70
5
Human Inborn Errors of Immunity in Pyoderma Gangrenosum: A Systematic Review.
PMID: 38951460
Am J Clin Dermatol Β· 2024
0.68